Hello. I have been through the tutorials and now I am working my way up through the puzzle structures. One thing that I have noticed is that as soon as I have accomplished a particular goal I am inmediately directed to the next puzzle. Evidently having fulfilled the requirements of the puzzle the proposed solution is a good solution. However, are there better solutions or a best solution? I ask this because presumably I could keep changing nucleotides and lowering the free energy (this I would think should be a better solution) until a point in which no changes to the sequence would lower the free energy, i.e., an absolute minimum and -I think- the best solution.
I am aware that reaching an absolute minimum is in practice extremely difficult because of the many degrees of freedom involved. However, what I don’t fully understand is why to submit one’s solution at the very point that the minimum structural requirements are met and not to let the person improve upon the structure until one considers that it is ready to be submitted. Hope I am making sense
Digital: That’s a great question! In EteRNA, there’s no such thing as a “better or worse” solution until you get into the Lab. In the tutorials, challenge, and player puzzles, the point is simply to create a solution that folds properly!
When you get into the lab, the goal of becomes to create RNAs which fold properly when actually synthesized. Every week when we get the synthesis data back, we do actually measure “how well” the RNA folded, and give it a score. But top players have long ago foregone free energy as the sole, or even most important determinant of proper folding. The ultimate goal of EteRNA is to figure these rules out. To see some of the great hypotheses which players have put forward, check out these message boards, or just head over to the strategy market.
Thanks Adrien for your thorough response. I’ll check the boards for the discussions you mentioned.
I have skimmed through the paper that is the basis of the ViennaRNA package that I understand is the basis for the free energy scoring. Forgive me if I am asking too naive questions but this is not my field:
The paper is somewhat old (1999). No one has come up with a better model or with more updated parameters since then?
I assume the databases used for the generation of the free energy functions are for structures in solution which I also assume are the structures you generate in the lab. Am I right?
The set of puzzles that want to maximize Red/Blue pairs do have better solutions, presumably, with more of the wanted pairs. These are frustrating for me because my preferred method would be to make a stable structure then add in Reds to Yellow/Blue pairs, and switch them around to maximize desired pairs. It would be nice to have a Wait button on these structures at least, to allow you to maximize the wanted pairings from a stable structure. In addition, in at least some of the other puzzles, I sort of arrived at a solution almost accidentally, and it would have been nice to have a wait there too. I know we can go back to the puzzles with the Stay, but as far as I can tell there is no way to re-submit a better solution from there, so no point gratification.
Hmm. Not sure what you’re suggesting here, but if you want to go back and see your solution, you can always click on the puzzle again and it will take you back to your previous solution.